Buprenorphine is a semi-synthetic opioid derivative of thebaine that is used to treat opioid addiction in higher dosages (>2 mg), to control moderate acute pain in non-opioid-tolerant individuals in lower dosages (˜200 μg), and to control moderate chronic pain in dosages ranging from 20-70 μg/hour.

Buprenorphine is available in a variety of formulations: SUBUTEX, SUBOXONE, ZUBSOLV (buprenorphine HCl and naloxine HCl; typically used for opioid addition), TEMGESIC (sublingual tablets for moderate to severe pain), BUPRENEX (solutions for injection often used for acute pain in primary-care settings), NORSPAN, and BUTRANS (transdermal preparations used for chronic pain).
As an opioid, buprenorphine lends itself to some uses for which it has not been approved by the drug regulatory agency of the country in which it is used (such as the U.S. FDA). One such off-label use (perhaps the most common) is the use of SUBUTEX or SUBOXONE, a formulation intended solely for the treatment of opioid abuse, in palliation of severe pain with no neuralgic component or when the neuralgia is otherwise treated, such as with pregabalin. Niche pain indications, for which SUBUTEX or SUBOXONE may be a medication of choice, include obstruction of the small bowel; continuous nasogastric suction; oesophageal fistula; malignancy in the head or neck; and other cases where the patient is unable to swallow or this is difficult. Additionally, SUBUTEX or SUBOXONE may be an interesting alternative to sustained-release opioids such as morphine (MS CONTIN) and oxycodone (TARGIN).
Furthermore, buprenorphine is somewhat sleep-inducing, and may be of particular help when pain leads to sleeplessness. Other prototypical opioid side-effects may prove beneficial in the management of chronic pain, such as its characteristic euphoria (to alleviate depression due to pain, or in cases where the patient cannot tolerate or is resistant to conventional thymoleptic antidepressants), as well as its anxiolytic effects. These effects manifest themselves chiefly when buprenorphine is used in patients not tolerant to opioids; use of a partial agonist such as buprenorphine in those tolerant or dependent will simply lead to precipitated withdrawal (if a different opioid is used concomitantly) or relief of withdrawal (if used as monotherapy).
There remains a need for process(es) for the preparation of intermediates in the synthesis of buprenorphine, which process(es) are suitably for large scale/commercial manufacture, preferably process(es) which require fewer steps and/or fewer distillations and/or fewer isolation steps than current processes, while maintaining or improving overall product yield and/or purity.